Prevalence of Allergy and Autoimmune Diseases are high in developed countries, but not in developing countries. Helminth infection were associated with lower level of allergy but the mechanism is not yet clear. In hygiene countries like UK, Japan and Korea, Fecal Microbiota Transplantation (FMT) has gained interest as novel therapy and prevention and reach to medicine industrial manufactures. This study will support it by associate Hygiene Hypothesis (HyHy) and the high prevalence of Allergy and Autoimmune Disease. Systematic review and Bayesian network analysis in EBSCO host search engine were used. Result from dynaMed Evidence Based, Point-of-care Reference e Journals: Dentistry, Medical and Nursing has describe 9 literatures support the association of Hy-hy/parasite infection with Allergy and/ or Autoimmune Diseases: 2 publications of meta-analysis are chosen and supported by 5 cross sectional, longitudinal, cause-effect design, and 2 clinical and animal trial. Conclusions: Low-middle-high income countries has a life style of Hyhy pattern support FMT industrial medicine and travelling to developing countries with broad diversity bacteria and worm in therapeutic and prevention potential, supported by sub-saharan and tropical rainforest developing countries.

1. International Journal of Environmental & Agriculture Research (IJOEAR) ISSN:[2454-1850] [Vol-3, Issue-5, May- 2017]
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Association of Hygiene Hypothesis with High prevalence of
Allergy and Autoimmune Diseases: FMT industry
Peni K Samsuria Mutalib1
, Mirna Nurasri Praptini2
, Mutalib Abdullah3
, Meny Hartati4
1
Department of Medical Physics, Faculty of Medicine, Universitas Indonesia, INDONESIA
2
Department of Internal Medicine, Gatot Subroto Hospital, Jakarta, INDONESIA
3
Unit Hemodialysis, Department of Internal Medicine, Tangerang District General Hospital, Banten, Universitas Indonesia,
INDONESIA
4
Departement of Pathology Anatomy, Faculty of Medicine, University of Indonesia, INDONESIA
Abstract—Prevalence of Allergy and Autoimmune Diseases are high in developed countries, but not in developing
countries. Helminth infection were associated with lower level of allergy but the mechanism is not yet clear. In hygiene
countries like UK, Japan and Korea, Fecal Microbiota Transplantation (FMT) has gained interest as novel therapy and
prevention and reach to medicine industrial manufactures. This study will support it by associate Hygiene Hypothesis
(HyHy) and the high prevalence of Allergy and Autoimmune Disease. Systematic review and Bayesian network analysis in
EBSCO host search engine were used. Result from dynaMed Evidence Based, Point-of-care Reference e Journals: Dentistry,
Medical and Nursing has describe 9 literatures support the association of Hy-hy/parasite infection with Allergy and/ or
Autoimmune Diseases: 2 publications of meta-analysis are chosen and supported by 5 cross sectional, longitudinal, cause-
effect design, and 2 clinical and animal trial. Conclusions: Low-middle-high income countries has a life style of Hyhy
pattern support FMT industrial medicine and travelling to developing countries with broad diversity bacteria and worm in
therapeutic and prevention potential, supported by sub-saharan and tropical rainforest developing countries.
Keywords— Hygiene hypothesis, allergy, autoimmune diseases, FMT industrial medicine, traveling to developing
countries.
I. INTRODUCTION
A firmed increase of global prevalence in allergic diseases mainly among children in the last few decades. Over the years,
where several epidemiological studies have reported an inverse association between parasitic worm infections and allergies.
The relationship between helminthes infection and allergies is urgent as research aims move to approach the potential of
therapy and prevention in using helminths and their products for allergic disorders.1
Using infectious disease high prevalence
countries as a source of prevention and treatment of allergy and autoimmune diseases (AD). Knowledge of much references
in the association of Hyhy-Allergy2,3,4
Molecular aspect of epitope mapping of bacteria and worm vs. lifestyle in low-middle-
high income population are associated with Most of Autoimmune Diseases are costly but Fecal Microbiota Transplantation
(FMT) is an effective potential therapy and vaccine.5
Traveling to developing countries with high biodiversity microbiota are
also promising.
II. MATERIAL AND METHOD
Systematic Review and Bayesian analysis using EBSCO host DynaMed: Evidence –Based, point-of Care Reference, e-
Journal: Dentistry, Medical and Nursing search engine. First, searching with CINAHL plus with developing the knowledge
for the aims of study. Using the following search terms: Autoimmune Diseases, Hygiene Hypothesis, Epidemiology and AD,
Atopic Sensitization, Asthma, T1D, IBS, MS, Rheumatoid Arthritis, Ulcerative Colitis, Allergic Diseases. Epidemiology
AND Autoimmune Disease and UK (263), AND Japan (259). FMT are growing (4550), FMT and Meta-analysis (12), FMT
and UK (34), FMT AND Japan (66). FMT industry (3), Hygiene Hypothesis AND Autoimmune Disease (117), Helminth
AND Autoimmune diseases (148), Worm and Autoimmune (36), Worm and Hygiene Hypothesis (17), Epidemiology AND
Meta-analysis and Rheumatoid Arthritis (27). Second step, all are screening abstract or title: excluded the not relevant and
the duplicates by Bayesian analysis. Since we were interested in explanatory factors of bacteria and worm epitope
sequencing are filtered. In the third step, screening full text publications, excluded since not relevant, duplicated and
extracted for Table. Association of Hygiene Hypothesis or parasite infection AND Allergy/ Autoimmune Diseases. The
selection was mainly performed by one reviewer and confirmed by the co-authors.

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III. DISCUSSIONS
3.1 Dry and Wet climate
From clinical to molecular aspect of inflammation markers in savanna (warm and dry climate) with dormant bacteria and
worm in dry season, and also in tundra (cold and dry) where no worm no bacteria in all season are searched by us.
Meanwhile AD have been found in low prevalence in wet and warm (tropical rainforest) or hot and humid (sub-Sahara)
countries, whereas allergy and AD are epidemic in clean countries. Dormant bacteria in dry season are specific physics-
chemistry antigens and broad spectrum of variable microbiota implies rich of epitope of protein from known FMT. Figure 1
of Flowchart and Table 1 showed the association of Hygiene Hypothesis with allergy and AD.1-2, 4-11
TABLE 1
DESCRIPTION OF IDENTIFIED 9 LITERATURES ON HYGIENE HYPOTHESIS(WORM-BACTERIA)-
ALLERGY/AUTOIMMUNE DISEASES
Study Design Population
Hygiene Hypothesis
autoimmune
measure
Epitope / synthetic
vaccine measure
Figueiredo 2013
Comparison of high
vs. low infection
Environmental condition in
Latin American
Aeroallergen
Immunologic
phenotypes, atopy,
asthma
Obeng 2014 Cross-sectional
1385 Ghanaian
Schoolchildren
Schistosome infection
Mite Atopy but not
wheeze & asthma
Hamid 2011 A longitudinal study
Semi urban and rural areas of
Flores, Indonesia
Intestinal helminth
infections
Allergy
Xu 2015
Randomized
Controlled Trial
(RCT)
Metabolic syndrome subjects
Fecal Microbiota
Transplantation
Beyond intestinal
disorders
Lopez-Isac 2016 Meta-analysis
Meta-genome-wide
association (meta-GWAS)
Systemic Sclerosis
(SSc) and Rheumatoid
Arthritis (RA)
Top single-nucleotide
polymorphism
Colman 2014
Systematic review
and Meta-analysis
18 studies of FMT primary
therapeutic agent for 122 pts
with 79 ulcerative colitis, 39
Crohn’s disease, 4 IBD
Clinical remission
and/or mucosal
healing
IBS as autoimmune
disease
Puentes F 2016
Animal model of
autoimmune disease
Tolerogenic potential of
fusion protein in 10
transgenic mouse model
Parasite proteins
containing repeats are
essential invasion
ligands
Ability to evade the
host immune system
Ajendra 2016 Experimental
NOD mice after insulitis
started in T1D process
Inflammation of the
pancreatic islets
Helminth antigens as a
new potential
therapeutic approach
against AD
Lagier 2014 Review
Longitudinal CT of
Recurrent CDI patients
FMT frozen, antigens
Extensive use and
wide industrialization
of FMT against AD

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FIGURE 1. FLOWCHART OF THE 9 IDENTIFIED LITERATURE: 2 META-ANALYSIS, 2 REVIEW, 3 CROSS
SECTIONAL, LONGITUDINAL, CAUSE-EFFECT DESIGN, 2 EXPERIMENTAL (ANIMAL/ AHUMAN) WHICH
ASSOCIATED HYGIENE HYPOTHESIS/PARASITE INFECTION WITH ALLERGY AND AUTOIMMUNE DISEASES
Improved hygiene and little infections in childhood influence the development of allergic and autoimmune diseases. It has
been reported in Latin America (Urban Brazil),6
a tropical rainforest area. Lifestyle factors with microbial exposure are
associated with allergy prevalence also reported in developed countries.7
Not only microbial exposure, helminth infections are also associated with low prevalence of allergy, 8,11
till FMT are used as
therapy in Autoimmune Diseases 12
Including metabolic diseases.9
Systematic sclerosis and rheumatoid arthritis has been identified have a common susceptibility
locus of gene.13
3.2 Proinflammatory cytokine as hygiene hypothesis marker
Parasite proteins contains repeats which induce immunosuppression and induce down-regulation of TNF- (cytokine
proinflammation) and TGF- (cytokine profibrosis) make potential application for the treatment and prevention of
autoimmune diseases.14
Entering of helminth antigens increase the protective effect stipulated by antigen-peculiar therapies and symbolizes a new
approach for potential therapy against AD including T1DM.15
The use of microbiota which has been frozen facilitates
transplantation, and per oral are at least as effective as other invasive methods and to keep from occurring the risk of
anesthesia. The use of pills form, already test as clinical trials, will certainly be the beginning landmark for the width use and
broad industrialization of fecal microbiota transplantation.10
Treatment with helminthes and worms ova mitigated the clinical symptoms of numbers autoimmune diseases in animal
model and in patients. Tuftsin-PC (TPC), a novel helminth-based compound, reduced proinflammatory cytokines and
induced the expression of anti-inflammatory cytokine, as well as expansion of Treg and Breg cells, also histological analysis
guide to a new approach for a natural therapy for beginning rheumatoid arthritis onset, one of autoimmune diseases.16
The role of transfer of immune cells adoption in worm-influenced regulation of allergy and autoimmune diseases, was
supported by animal experiments.17
The chronic diseases for families economic burden, health systems, governments and the
association between national policy maker and international economic pressure and politics have a large impact on chronic
diseases risk and countries ability in responding them, the potential of wet and warm climate area double burden of infectious
and chronic diseases.18
9 Publications of meta-analysis AND Hygiene Hypothesis/FMT AND Autoimmune diseases
Meta-analysis
1. Okada RA MA (12): 2016
2. Kim RA MA (31): 2017
3. Orenstein AE AND IBS AND MA (4): 2010
4. helminth AND autoimmune (277) + 2: 2017
EBSCO: CINA HL plus
(Medline/PubMed) with full text
FMT^MA (11): 2016
Helminth^AD (148): 2017
Worm^AD (36): 2017
Worm^HyHy (17): 2016
Epitope^Helminth^Vaccine (82): 2017
Bacteria envelope and wall of
worm cells range of Epitopes
(Antigen and Antibody): Epitope
AND Meta-analysis AND RA (27):
2016
Screening abstract or title: 294-256
excluded since not relevant or
duplicates analyzed by Bayesian
network
Screening abstract or title: 27-
20 excluded since not relevant
or duplicates analyzed by
Bayesian network
Screening abstract or title: 48-30 excluded
since not relevant or duplicates analyzed
by Bayesian network
Screening full test: 54 excluded since not relevant

4. International Journal of Environmental & Agriculture Research (IJOEAR) ISSN:[2454-1850] [Vol-3, Issue-5, May- 2017]
Page | 65
3.3 Economic income and Hygiene Hypothesis
How the present of chronic conditions in certain multimorbidity patterns, which could have great burden on public health at
several levels in low-, middle,-, and high-income countries has been identify and describe in several countries to the
advancement of preventive actions to decrease their prevalence and also give increase to new, understandable approaches for
the management of these co-existing conditions. 19
The association of individuals raised in hygiene environment have a higher of developing Allergy and Autoimmune Diseases
was supported by random or fixed-effect meta-analyses.20
IV. LIMITATION
These Systematic review has several limitation 1) Non published literature on all autoimmune diseases may limit the validity
of our findings, but these inflammatory bowel diseases and rheumatoid arthritis study are a real phenomenon which is
already attracted peoples from developed and clean countries with AD burden. However, we used meta-analysis with partly
overlapping data bases for our literature search on bacteria and worm cell wall antigens. And we found a large number of
papers fulfilling the criteria of our search in these HyHy-AD prevention and therapeutic. 2) Another potential problem in
this systematic review is that studies mainly used in the searching steps are depended on the vocabulary synonyms (not find
in general, but many in specific such as autoimmune diseases could be Rheumatoid arthritis, recurrent CDI, IBS, T1D, atopic
sensitization, asthma etc.) but not in Lupus Erythematosus. Different chances changes choices used give different results
may be misleading. We intended to manage this problem in an additional work, by dividing the using chosen specific to
generic into 2 broad categories: prevention and therapeutic findings.
V. SUMMARY
Epitope of FMT, bacteria, wall of worm are all rich of ranges epitopes and could be present in therapeutic a prevention
potential. These epidemiological studies from developing/ tropical rainforest area countries, present to hygiene developed
countries is similarly paralleled with low-middle- high- income population, vaccination and therapeutic fighting against
autoimmune diseases. Hygiene hypothesis / FMT has association with novel treatment for Allergy and Autoimmune
Diseases. Further knowledge and education to policy maker and global politic doer from local to global will support the
industries in FMT.
VI. CONCLUSION
Low-middle-high income countries has a life style of Hygiene hypothesis. The low- and middle economic income in
development countries have similar pattern with population in developing countries, which support FMT industrial medicine
and travelling to developing countries. Broad diversity bacteria and worm in therapeutic and prevention potential, supported
by sub-saharan and tropical rainforest developing countries.
ACKNOWLEDGEMENTS
We thank DRPM University of Indonesia, for the funding of specific stuff exposure in wet and warm/ hot and humid climate
DRPM UI 2015 no. 1772/UN2.R12/HKP.05.00/2015 and 240BE/DRPM-UI/NI.4/2008 and IMERI 2016 abstract send no.
5229. To Aaron Jonathan, we thank for supporting in the poster presentation.
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